Rationale and design of XAMOS: noninterventional study of rivaroxaban for prophylaxis of venous thromboembolism after major hip and knee surgery.

Venous thromboembolism is a frequent and potentially life-threatening complication of orthopedic surgery. Rivaroxaban is an oral direct factor Xa inhibitor, which was shown to be effective for the prevention of venous thromboembolism after elective hip and knee arthroplasty in the RECORD study program. Rivaroxaban has the potential to overcome the limitations of the current standards of care in the prevention of venous thromboembolism. XAMOS (Xarelto(®) in the prophylaxis of post-surgical venous thromboembolism after elective major orthopedic surgery of hip or knee) is an international, noninterventional, parallel-group study to gain insight into the safety (major bleeding, side effects) and effectiveness (prevention of symptomatic thromboembolic events) of rivaroxaban in daily clinical practice. XAMOS will follow 15,000 patients after major orthopedic surgery in approximately 200 centers worldwide, with about 7500 patients receiving rivaroxaban and about 7500 standard of care. XAMOS will supplement the clinical data obtained in the Phase III RECORD 1, 2, 3, and 4 trials in which rivaroxaban was shown to be superior for the primary efficacy endpoints, and with a safety profile similar to that of enoxaparin after hip or knee replacement surgery. XAMOS was started in 2009 and will complete recruitment and follow-up in 2011.

Effects of the vasodilating beta-blocker nebivolol on smoking-induced endothelial dysfunction in young healthy volunteers.

OBJECTIVE: To assess the effect of nebivolol, a highly selective third generation beta1-adrenoceptor antagonist with an endothelium-dependent vasodilatory action, on smoking-induced endothelial dysfunction. RESEARCH DESIGN AND METHODS: This open-label study examined the effect of 14 daily doses of 5 mg nebivolol on forearm blood flow in 21 healthy, young, male, light smokers (< or =5 cigarettes/day), measured by plethysmography on Days 1, 7, and 14. The primary endpoint was the difference in forearm blood flow after smoking one standard cigarette from baseline (Day 1) until treatment end on Day 14. Secondary outcomes included the difference in forearm blood flow between Day 1 and Day 7 compared with Day 14 before and after smoking, the effect of nebivolol on blood coagulation parameters, high-sensitive-C-reactive protein (hs-CRP), and the safety and tolerability of nebivolol. RESULTS: Nebivolol for 14 days did not significantly affect forearm blood flow after smoking. On Day 7 of nebivolol treatment, forearm blood flow after smoking was significantly greater than blood flow before smoking (increase of 0.44 mL/min; p = 0.00656). Serum level ofhs-CRP showed a marked decrease from Day 1 to Day 14. No changes in coagulation parameters were observed over the course of nebivolol treatment. Nebivolol was well tolerated throughout the study. CONCLUSIONS: The increase in forearm blood flow and the marked decrease in hs-CRP over 14 days of treatment suggest that nebivolol has a positive effect on endothelial function in light smokers, but larger studies are required to confirm these observations.

Quality of life in hypertension management using olmesartan in primary care.

OBJECTIVE: Differences in quality of life (QoL) using antihypertensive drugs may account for differences in compliance, persistence and blood pressure control. As this is the prerequisite for cardiovascular risk reduction, QoL was investigated using highly tolerable drugs (such as olmesartan). RESEARCH DESIGN/METHODS: The non-interventional study was carried out in 4252 primary care patients with 6 weeks of follow up. Documentation of patient characteristics included concomitant diseases and antihypertensive medication, blood pressure, pulse pressure, pulse rate and evaluation of QoL using the SF-12 questionnaire. Comparison of data at 6 weeks after adding or switching to olmesartan treatment (median dose: 20 mg) with baseline values. MAIN OUTCOME MEASURES: Patients had mild-to-moderate hypertension, 52.6% of whom were male and the mean age was 60.5 +/- 11.9 years. Dyslipidaemia (38.3%), diabetes (20.9%) and coronary heart disease (16.4%) were the most frequent concomitant diseases. After 6 weeks, blood pressure was reduced by -22.8 +/- 14.1/-11.5 +/- 8.3 mmHg (p < 0.001 versus baseline). All items of the SF-12 questionnaire and both sum scores improved over the course of treatment (p < 0.001 versus baseline), and were well compatible with non-hypertensive controls. Improvements were higher when switching from alpha-blockers, calcium channel blockers, beta-blockers, diuretics and angiotensin-converting enzyme inhibitors as compared with angiotensin II type 1 receptors blockers (ARBs), in particular on the mental health scale (p < 0.001). Adverse events were rare (0.66%), with dizziness (n = 8; 0.19%) being the most frequent. CONCLUSIONS: As was shown in the current study, patients on olmesartan treatment not only achieve adequate blood pressure control but also experienced a substantial improvement of QoL. This may contribute to long-term blood pressure control using ARBs.

Blood pressure-lowering effect of nebivolol in hypertensive patients with type 2 diabetes mellitus: the YESTONO study.

BACKGROUND: Effective blood pressure (BP)-lowering therapy is regarded as the most important intervention in diabetes mellitus. Nebivolol is commonly used for the treatment of hypertension, but to date there has been no study of its use in a large population of hypertensive patients with type 2 diabetes mellitus. METHODS: A prospective, open-label, multicentre, post-marketing surveillance study was conducted in 2838 patients with arterial hypertension requiring intervention and concomitant type 2 diabetes, with or without other diseases. The therapeutic agent was nebivolol, either as monotherapy or as add-on therapy to other antihypertensive agents, over a minimum period of 3 months, with the primary endpoint being achievement of target BPs, that is, systolic BP < or = 140 mm Hg and diastolic BP < or = 90 mm Hg. Other endpoints were changes in metabolic parameters, effects on physical capability and tolerability during treatment. Statistical analysis was prospectively planned and conducted on an intention-to-treat basis. RESULTS: Mean (SD) BP decreased from 156 (15.3)/92 (9.4)mm Hg to 135 (11)/81 (6.6)mm Hg during the treatment period, while mean (SD) heart rate decreased from 79 (10) to 71 (7) beats/min. Strict reduction of BP was associated with improvements in most metabolic parameters, including lipid levels, glycosylated haemoglobin (HbA(1c)) and microalbuminuria. Maximum physical capability improved modestly. Most patients (85%) received nebivolol 5 mg/day. CONCLUSIONS: Strict BP reduction in hypertensive patients with type 2 diabetes with or without other concomitant cardiovascular diseases is achieved with nebivolol 5 mg/day in most patients. The benefits of lowering BP with use of nebivolol are associated with improvements in most metabolic parameters and in maximum physical capability.